NeoplasmsPhase 1NCT04526509
Master Protocol to Assess Safety and Dose of First Time in Human Next Generation Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Advanced Solid Tumors
A Phase 1 study testing GSK3901961, GSK3845097 and GSK4427296 in people with Neoplasms, run by Adaptimmune at 17 sites in 6 countries.
Trial summary
This trial will evaluate the safety and efficacy of first time in human engineered T-cell therapies, in participants with advanced tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- GSK3901961, GSK3845097 and GSK4427296
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 17 sitesin 6 countries
- Study dates
- 21 Dec 2020to 8 Jun 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant must be >=18 years of age and weighs ≥40 kg on the day of signing informed consent
- Participant must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles
- Participant's tumor must have tested positive for NY-ESO-1 and/or LAGE-1a expression by a GSK designated laboratory
- Performance status: Eastern Cooperative Oncology Group of 0-1
- Participant must have adequate organ function and blood cell counts 7 days prior to leukapheresis
- Participant must have measurable disease according to RECIST v1.1.
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- Additional criteria for participants with SS/ MRCLS:
- Participant has advanced (metastatic or unresectable) SS or MRCLS confirmed by local histopathology with evidence of disease-specific translocation
- Participant has completed at least one standard of care (SOC) treatment including anthracycline containing regimen unless intolerant to or ineligible to receive the therapy. Participants who are not candidates to receive anthracycline should have received ifosfamide unless also intolerant to or ineligible to receive ifosfamide. Participants who received neoadjuvant/adjuvant anthracycline or ifosfamide based therapy and progressed will be eligible
- Additional criteria for participants with non-small cell lung cancer (NSCLC):
- Participant has Stage IV NSCLC as confirmed by histology or cytology
- Prior therapies for participants lacking actionable genetic aberrations (i.e., wild type), per National Comprehensive Cancer Network (NCCN) guidelines: participant has been previously treated with or is intolerant to programmed death receptor-1 (PD)-1/Programmed death ligand 1 (PD-L1) checkpoint blockade therapy and has been previously treated with or is intolerant to a platinum-based chemotherapy. Adjuvant therapy will count as a regimen if completed within 6 months before relapse. Or for participants that harbors an actionable genetic aberration (e.g. BRAF, anaplastic lymphoma kinase [ALK]/ c-ros oncogene 1 [ROS1] etc.), per NCCN guidelines: participants has been previously treated with or is intolerant to SOC therapy, including targeted therapy, as recommended by NCCN or equivalent country-level guidelines (European Society for Medical Oncology [ESMO], National Institute for Health \& Care Excellence [NICE]) . Or Investigator has decided that additional lines of SOC therapy after the first line are not in the participant's best interest.
Who cannot join
- Central nervous system (CNS) metastases, with certain exceptions for CNS metastases in NSCLC as specified in the protocol
- Any other prior malignancy that is not in complete remission
- Clinically significant systemic illness
- Prior or active demyelinating disease
- History of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments
- Previous treatment with genetically engineered NY-ESO-1-specific T cells, NY-ESO-1 vaccine or NY-ESO-1 targeting antibody
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- Prior gene therapy using an integrating vector
- Previous allogeneic hematopoietic stem cell transplant within the last 5 years or solid organ transplant
- Washout periods for prior radiotherapy and systemic chemotherapy must be followed
- Major surgery within 4 weeks prior to lymphodepletion
- Pregnant or breastfeeding females
Trial locations and contacts
17 sites in 6 countries.
17 sites in 6 countries
United States9 sites
GSK Investigational Site
Atlanta, Georgia, 30322
GSK Investigational Site
Baltimore, Maryland, 21287
GSK Investigational Site
Houston, Texas, 77030
GSK Investigational Site
Jacksonville, Florida, 32224
GSK Investigational Site
Lexington, Kentucky, 40536
GSK Investigational Site
New York, New York, 10032
GSK Investigational Site
New York, New York, 10065
GSK Investigational Site
St Louis, Missouri, 63110
GSK Investigational Site
Westwood, Kansas, 66205
Germany3 sites
GSK Investigational Site
Cologne, North Rhine-Westphalia, 50937
GSK Investigational Site
Dresden, Saxony, 01307
GSK Investigational Site
Munich, Bavaria, 81377
Canada2 sites
GSK Investigational Site
Montreal, Quebec, H1T 2M4
GSK Investigational Site
Toronto, Ontario, M5G 2M9
About this study
Official title: Master Protocol to Assess the Safety and Recommended Phase 2 Dose of Next Generations of Autologous Enhanced NY-ESO-1/ LAGE-1a TCR Engineered T-cells, Alone or in Combination With Other Agents, in Participants With Advanced Tumors
This trial will evaluate the safety and efficacy of first time in human engineered T-cell therapies, in participants with advanced tumors.
Read the detailed description
This study is a master protocol. It has two sub studies registered as 209012 Sub Study 1 (NCT06048705) and 209012 Sub Study 2 (NCT05943990).
- Conditions
- Neoplasms
- Being tested
- GSK3901961, GSK3845097, GSK4427296, Cyclophosphamide, Fludarabine
- Keywords
- Adoptive T-cell therapy, Advanced synovial sarcoma, Advanced non-small cell lung cancer, Advanced tumors, GSK3845097, GSK3901961, GSK4427296, T cell receptors, Leukapheresis, Advanced myxoid/round cell liposarcoma
- Medical subject headings
- Neoplasms, Liposarcoma, Myxoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK3901961Drug
GSK3901961 as an IV infusion.
GSK3845097Drug
GSK3845097 as an IV infusion.
GSK4427296Drug
GSK4427296 as an IV infusion.
CyclophosphamideDrug
Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.
FludarabineDrug
Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.
| Study group | Role | What they receive |
|---|---|---|
| Substudy 1: Cohort 1 - GSK3901961 in previously treated metastatic NSCLC | Experimental | Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as intravenous (IV) infusion after completing lymphodepleting chemotherapy. Receives: Drug: GSK3901961; Drug: Cyclophosphamide; Drug: Fludarabine |
| Substudy 1: Cohort 2 - GSK3901961 in previously treated advanced SS or MRCLS | Experimental | Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as IV infusion after completing lymphodepleting chemotherapy. Receives: Drug: GSK3901961; Drug: Cyclophosphamide; Drug: Fludarabine |
| Substudy 2: GSK3845097 in previously treated advanced SS or MRCLS | Experimental | Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3845097, as IV infusion after completing lymphodepleting chemotherapy. Receives: Drug: GSK3845097; Drug: Cyclophosphamide; Drug: Fludarabine |
| Substudy 3: GSK4427296 in previously treated advanced SS or MRCLS | Experimental | Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK4427296, as IV infusion after completing lymphodepleting chemotherapy. Receives: Drug: GSK4427296; Drug: Cyclophosphamide; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Enrolled Across Sub Studies
Number of Participants Randomized across sub studies are presented.
Measured: Day -7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2020
- Study start21 Dec 2020
- Primary completion8 Jun 2023
- Study completion8 Jun 2023
Why it stopped: The study was terminated due to a change in GSK's R\&D priorities.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Adaptimmune
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Adaptimmune Patient Enquiries, Principal investigator, Adaptimmune
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04526509
- Sponsor's protocol ID
- 209012
- Other IDs
- 2019-004446-14, 2019
- Status last verified
- Nov 2024
- First submitted
- 21 Aug 2020
- Last updated
- 26 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Master Protocol to Assess the Safety and Recommended Phase 2 Dose of Next Generations of Autologous Enhanced NY-ESO-1/ LAGE-1a TCR Engineered T-cells, Alone or in Combination With Other Agents, in Participants With Advanced Tumors
- ClinicalTrials.gov ID
- NCT04526509
- Acronym / sponsor ID
- 209012
- Conditions
- Neoplasms
- Keywords
- Adoptive T-cell therapy, Advanced synovial sarcoma, Advanced non-small cell lung cancer, Advanced tumors, GSK3845097, GSK3901961, GSK4427296, T cell receptors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to a change in GSK's R\&D priorities.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- AdaptimmuneIndustry (pharma, biotech, devices)
- Study start
- 21 Dec 2020 (actual)
- Primary completion
- 8 Jun 2023 (actual)
- Study completion
- 8 Jun 2023 (actual)
- First posted
- 25 Aug 2020 (actual)
- Results
- Posted 10 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial will evaluate the safety and efficacy of first time in human engineered T-cell therapies, in participants with advanced tumors.
Detailed description
This study is a master protocol. It has two sub studies registered as 209012 Sub Study 1 (NCT06048705) and 209012 Sub Study 2 (NCT05943990).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Substudy 1: Cohort 1 - GSK3901961 in previously treated metastatic NSCLC | Experimental | Drug: GSK3901961, Drug: Cyclophosphamide, Drug: FludarabineEligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as intravenous (IV) infusion after completing lymphodepleting chemotherapy. |
| Substudy 1: Cohort 2 - GSK3901961 in previously treated advanced SS or MRCLS | Experimental | Drug: GSK3901961, Drug: Cyclophosphamide, Drug: FludarabineEligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as IV infusion after completing lymphodepleting chemotherapy. |
| Substudy 2: GSK3845097 in previously treated advanced SS or MRCLS | Experimental | Drug: GSK3845097, Drug: Cyclophosphamide, Drug: FludarabineEligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3845097, as IV infusion after completing lymphodepleting chemotherapy. |
| Substudy 3: GSK4427296 in previously treated advanced SS or MRCLS | Experimental | Drug: GSK4427296, Drug: Cyclophosphamide, Drug: FludarabineEligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK4427296, as IV infusion after completing lymphodepleting chemotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Participant must be >=18 years of age and weighs ≥40 kg on the day of signing informed consent
- Participant must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles
- Participant's tumor must have tested positive for NY-ESO-1 and/or LAGE-1a expression by a GSK designated laboratory
- Performance status: Eastern Cooperative Oncology Group of 0-1
- Participant must have adequate organ function and blood cell counts 7 days prior to leukapheresis
Key exclusion criteria (11 listed)
- Central nervous system (CNS) metastases, with certain exceptions for CNS metastases in NSCLC as specified in the protocol
- Any other prior malignancy that is not in complete remission
- Clinically significant systemic illness
- Prior or active demyelinating disease
- History of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK3901961GSK3901961 as an IV infusion. | Drug | Substudy 1: Cohort 1 - GSK3901961 in previously treated metastatic NSCLC, Substudy 1: Cohort 2 - GSK3901961 in previously treated advanced SS or MRCLS |
| GSK3845097GSK3845097 as an IV infusion. | Drug | Substudy 2: GSK3845097 in previously treated advanced SS or MRCLS |
| GSK4427296GSK4427296 as an IV infusion. | Drug | Substudy 3: GSK4427296 in previously treated advanced SS or MRCLS |
| CyclophosphamideCyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route. | Drug | Substudy 1: Cohort 1 - GSK3901961 in previously treated metastatic NSCLC, Substudy 1: Cohort 2 - GSK3901961 in previously treated advanced SS or MRCLS, Substudy 2: GSK3845097 in previously treated advanced SS or MRCLS, Substudy 3: GSK4427296 in previously treated advanced SS or MRCLS |
| FludarabineFludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route. | Drug | Substudy 1: Cohort 1 - GSK3901961 in previously treated metastatic NSCLC, Substudy 1: Cohort 2 - GSK3901961 in previously treated advanced SS or MRCLS, Substudy 2: GSK3845097 in previously treated advanced SS or MRCLS, Substudy 3: GSK4427296 in previously treated advanced SS or MRCLS |
Primary outcome
Number of Participants Enrolled Across Sub Studies
Time frame: Day -7
Number of Participants Randomized across sub studies are presented.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adaptimmune Patient Enquiries principal investigator
Adaptimmune
17 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK3901961, GSK3845097 and GSK4427296 in people with Neoplasms, run by Adaptimmune at 17 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Germany, Canada, Australia, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Enrolled Across Sub Studies (time frame: Day -7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2024.